Heart failure (HF) and atrial fibrillation (AF) are the most common manifestations of cardiovascular disease in chronic kidney disease (CKD Over 40 million patients have CKD in the U.S. of which 30% develop HF and 15- 25% develop AF. Among CKD patients with HF, the incidence of preserved ejection fraction (PEF)-HF exceeds that of reduced ejection fraction (REF)-HF. Even the absence of clinical HF or AF, 75% of patients with CKD have left ventricular disease, 30% have abnormal electrocardiograms and ~50% have HF symptoms, all of which are associated with development of HF and AF. HF and AF often occur simultaneously, thus it is plausible that they may be interrelated through shared mechanistic pathways. Better understanding of the pathogenesis of HF and AF may identify possible therapeutic targets to improve current treatment for these diseases in CKD. The pathophysiology of cardiovascular disease is unique in CKD in part due to novel CKD-specific risk factors and metabolic effects of decreased clearance. Several promising biological pathways have been implicated in the pathogenesis of HF and AF in the general population and may be applicable to CKD including: myocardial ischemia, myocardial stretch, myocardial fibrosis and inflammation. Circulating cardiac biomarkers present an opportunity to understand these mechanistic pathways in humans. NT-proBNP is secreted from myocytes in response to myocardial stretch from pressure or volume overload. Troponin T rises in response to myocardial injury or remodeling. Galectin-3 is a beta-galactoside-binding lectin expressed by macrophages that induces cardiac fibroblasts, promoting myocardial fibrosis and adverse remodeling. Soluble ST2 (sST2) is a member of the IL-1 receptor family that promotes cardiomyocyte hypertrophy and myocardial fibrosis. Growth differentiation factor (GDF)-15 is a TGF-beta cytokine that increases in response to myocyte ischemia, mechanical stretch and proinflammatory cytokines. CKD-specific risk factors may lead to differences in these promising biological pathways in CKD, thus warranting specific evaluation in this population. The overall goal of this proposal is to test the association of these biomarkers with clinical HF and AF and with intermediate measures of subclinical disease to understand the biological underpinnings and pathogenesis of HF and AF in CKD. In the proposed study, we aim to test the hypothesis that biomarkers of myocardial ischemia, myocardial stretch, myocardial fibrosis and inflammation are associated with incident HF (particularly PEF-HF), HF symptoms and intermediate subclinical measures of HF (Aim 1) among participants with CKD in the Chronic Renal Insufficiency Cohort study. We will also test the hypothesis that these biomarkers are associated with incident AF and intermediate subclinical measures of AF among CRIC participants (Aim 2).